Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with the likelihood of distant metastasis to the liver or lungs adding to the challenges of CRC treatment. Currently, surgical resection and chemotherapy are the two main treatment modalities for colorectal cancer.
In recent years, emerging immune checkpoint blockade (ICB) therapy has provided new options for late-stage cancer patients. However, the efficacy of ICB therapy in CRC is limited. Mechanistically, effective ICB therapy relies mainly on CD8+ T cells. Strategies aimed at reducing the metastatic potential of colorectal cancer cells and promoting the infiltration and effector function of CD8+ T cells may be crucial for improving clinical outcomes in colorectal cancer patients.
Recently, researchers from Southern Medical University published an article titled “Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion” in the journal Int J Biol Sci, revealing CD73 as a promising target for treating colorectal cancer.
The limited benefits of metastasis and immune checkpoint blockade are two obstacles in combating colorectal cancer (CRC). CD73, encoded by the gene 5′-nucleotidase Ecto (NT5E), is the primary enzyme responsible for generating extracellular adenosine. However, the impact of CD73 on colorectal cancer progression and immune response remains unclear.
Here, researchers evaluated the clinical significance of CD73 in human colorectal cancer specimens using immunohistochemistry and bioinformatics analysis. The study demonstrated elevated CD73 levels in colorectal cancer tissues, particularly in metastatic colorectal cancer tissues, and its association with poor prognosis. Functional gain and loss experiments indicated that tumor CD73 supports tumor progression and impairs the vitality and effector function of CD8+ T cells. Targeting CD73 in CRC cells can reduce their malignant phenotype and enhance the anti-cancer response of CD8+ T cells in the tumor microenvironment (TME). Additionally, combination therapy with CD73 blockade and PD-1 inhibitors showed stronger anti-cancer effects compared to monotherapy.
In conclusion, clinical trials using ICBs as monotherapy have shown very poor complete response rates, emphasizing the importance of developing novel combination therapies that achieve an ideal balance between tumor immunity and autoimmunity. This study highlights the advantages of CD73 inhibition in preventing malignant transformation of CRC cells and restoring anti-tumor CD8+ T cell activity, providing a unique and effective approach for upcoming clinical trials in refractory CRC.
Reference
1. Lian, Weidong, et al. “Dual role of CD73 as a signaling molecule and adenosine-generating enzyme in colorectal cancer progression and immune evasion.” International Journal of Biological Sciences 20.1 (2024): 137..